MicroRNA expression profile in TSC cell lines and the impact of mTOR inhibitor

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Abstract The aim of this study was to assess the potential implication of microRNA on tuberous sclerosis (TSC) pathogenesis by performing microRNA profiling on cell lines silencing TSC1 or TSC2 genes using qPCR panels, before and after incubation with rapamycin. (Qiagen). Significant differences in expression were observed between samples before and after rapamycin treatment in 19 miRNAs in TSC1, five miRNAs in TSC2 and seven miRNAs in controls. Of six miRNAs dysregulated before rapamycin treatment in the TSC1 group, three normalized after treatment (miR-21-3p, miR-433-3p, let-7g-3p). Of three miRNAs dysregulated before rapamycin incubation in TSC2 group, one normalized after treatment (miR-1224-3p). Of the miRNAs dysregulated before rapamycin treatment in TSC1 and TSC2 group, two did not normalize after treatment (miR-33a-3p, miR-29a-3p). The results of the possible targets indicated that there are four common genes with seed regions susceptible to the regulation by those miRNAs: ZBTB20, PHACTR2, PLXNC1 and ATP1B4. Our data show no changes in mRNA expression of these targets before rapamycin treatment. These data suggest that miRNA may play a pivotal role in TSC pathogenesis. Some may serve as biomarkers of treatment efficacy. The variability of miR-29a-3p and miR-33a-3p after rapamycin treatment and the lack of changes in their downstream regulatory targets suggests that they might be mTOR independent.

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